DESCRIPTION: The broad objective of this application is to explore and define the mechanisms by which the autonomic nervous system regulates the circulation to support tissue perfusion, particularly in the brain, during adaptation to microgravity and readaptation to earth's gravity. The primary hypothesis is that adaptation to the unique environment of microgravity causes alterations in the autonomic nervous system that interact with microgravity-induced changes in body fluid distribution, that result in orthostatic intolerance upon return to earth. The unique characteristics of microgravity may modify neural afferent traffic and produce conflicting information. Microgravity minimizes the dynamic demands on the cardiovascular neural control. The level of physical activity is decreased, and no postural adjustments are required. This regulatory environment is likely to degrade important control mechanisms. The proposed experimental design represents and integrated approach to the testing of this primary hypothesis. The following working hypotheses will address: (1) whether efferent sympathetic nerve activity increases appropriately in response to baroreflex and non-baroreflex- mediated stimuli after space flight; (2) whether integrated clinical tests of autonomic function can detect functional impairment for use to characterize the time course of adaptation to microgravity; (3) whether regulation of the cerebral circulation changes are parallel to or independent of the regulation of the systemic circulation; and (4) whether advanced mathematical models of neural control, including both linear and non-linear dynamics, can be developed to gain insight into the integration among neurocirculatory variables and control mechanisms.